Cholesterol and Alzheimer's disease

Abstract

Accumulation of a 40–42-amino acid peptide, termed amyloid-β peptide (Aβ), is associated with Alzheimer's disease (AD), and identifying medicines that inhibit Aβ could help patients with AD. Recent evidence suggests that a class of medicines that lower cholesterol by blocking the enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase), termed statins, can inhibit Aβ production. Increasing evidence suggests that the enzymes that generate Aβ function best in a high-cholesterol environment, which might explain why reducing cholesterol would inhibit Aβ production. Studies using both neurons and peripheral cells show that reducing cellular cholesterol levels, by stripping off the cholesterol with methyl-β-cyclodextrin or by treating the cells with HMG-CoA reductase inhibitors, decreases Aβ production. Studies performed on animal models and on humans concur with these results. In humans, lovastatin, an HMG-CoA reductase inhibitor, has been shown to reduce Aβ levels in blood of patients by up to 40%. The putative role of Aβ in AD raises the possibility that treating patients with statins might lower Aβ, and thereby either delay the occurrence of AD or retard the progression of AD. Two large retrospective studies support this hypothesis. Both studies suggest that patients taking statins had an approx. 70% lower risk of developing AD. Since statins are widely used by doctors, their ability to reduce Aβ offers a putative therapeutic strategy for treating AD by using medicines that have already been proved safe to use in humans.